Spatial averaging for small molecule diffusion in condensed phase environments

The Journal of Chemical Physics

Doll

Dupuis

et al. 2011

Self Cite

120

We describe a new approach to the rare-event Monte Carlo sampling problem. This technique utilizes a symmetrization strategy to create probability distributions that are more highly connected and, thus, more easily sampled than their original, potentially sparse counterparts. After discussing the formal outline of the approach and devising techniques for its practical implementation, we illustrate the utility of the technique with a series of numerical applications to Lennard-Jones clusters of varying complexity and rare-event character.

Section: Background and Observationsmentioning

confidence: 99%

An infinite swapping approach to the rare-event sampling problem

The Journal of Chemical Physics

Doll

Dupuis

et al. 2011

Self Cite

120

“…Despite intense work, fundamental physico-chemical properties, such as the CO rebinding and migration barriers after photodissociation, are still poorly understood. Although the different pockets accessible to small diatomic ligands are well characterized by experiment (2)(3)(4)(5) and theory/computer simulations (6)(7)(8)(9), the pathways between the pockets and the energy barriers associated with them are more debatable. A full characterization of these properties requires direct sampling of the entire free energy surface.…”

Section: Introductionmentioning

confidence: 99%

“…For these reasons, MC and MD sampling are used to determine ligand positions in different parts of the substate space that provide initial positions for umbrella sampling from which quantitative data on the free energy barriers can be obtained. The possible positions for unbound ligands inside Mb have been previously characterized by experiment and simulations (2,(7)(8)(9)12,20) and the pockets and pathways connecting them are shown in Fig. 1.…”

Section: Introductionmentioning

confidence: 99%

Quantifying the Importance of Protein Conformation on Ligand Migration in Myoglobin

Meuwly

2012

Biophysical Journal

Self Cite

Myoglobin (Mb) is a model system for ligand binding and migration. The energy barriers (ΔG) for ligand migration in Mb have been studied in the past by experiment and theory and significant differences between different approaches were found. From experiment, it is known that Mb can assume a large number of conformational substates. In this work, these substates are investigated as a possible source of the differences in migration barriers. We show that the initial structure significantly affects the calculated ΔG for a particular transition and that fluctuations in barrier heights δΔG are of similar magnitude as the free energy barriers themselves. The sensitivity of ΔG to the initial structure is compared to other sources of errors. Different protein structures can affect the calculated ΔG by up to 4 kcal/mol, whereas differences between simple point charge models and more elaborate multipolar charge models for the CO-ligand are smaller by a factor of two. Analysis of the structural changes underlying the large effect of the conformational substate reveals the importance of coupling between protein and ligand motion for migration.

“…32,43 The chosen MC movesuch as translation or rotationis then applied to all M ε *N ε configurations and the corresponding energies E new (m,n) are determined. Two sets of Boltzmann weights are then computed, one for the old and one for the new configurations: E old,Boltz …”

Section: Methodsmentioning

confidence: 99%

Spatial Averaging: Sampling Enhancement for Exploring Configurational Space of Atomic Clusters and Biomolecules

Hédin

J. Chem. Theory Comput.

Doll

et al. 2014

Self Cite

Spatial averaging Monte Carlo (SA-MC) is an efficient algorithm dedicated to the study of rare-event problems. At the heart of this method is the realization that from the equilibrium density a related, modified probability density can be constructed through a suitable transformation. This new density is more highly connected than the original density, which increases the probability for transitions between neighboring states, which in turn speeds up the sampling. The first successful investigations included the diffusion of small molecules in condensed phase environments and characterization of the metastable states of the migration of the CO ligand in myoglobin. In the present work, a general and robust implementation including rotational and torsional moves in the CHARMM molecular modeling software is introduced. Also, a procedure to estimate unbiased properties is proposed in order to compute thermodynamic observables. These procedures are suitable to study a range of topical systems including Lennard-Jones clusters of different sizes and the blocked alanine dipeptide (Ala)2 in implicit and explicit solvent. In all cases, SA-MC is found to outperform standard Metropolis simulations in sampling configurational space at little extra computational expense. The results for (Ala)2 in explicit solvent are in good agreement with previous umbrella sampling simulations.